ABSTRACT: If approved, oncologists will have a new therapeutic option with proven benefits, acceptable toxicity, said EMBRACE trial leader.

There is new hope for women with locally recurrent or metastatic breast cancer who fail conventional therapies. In the phase III EMBRACE study, eribulin mesylate (E7389) improved overall median survival by 23%, compared with conventional treatment.

"There previously was no accepted single treatment of women with heavily pretreated metastatic breast cancer and no prior studies showing a survival benefit," said lead investigator Christopher Twelves, MD, professor of clinical pharmacology and oncology, and head of the Clinical Cancer Research Groups at the University of Leeds & St. James's Institute of Oncology in the UK. Now, "if or when approved, practicing oncologists will have a therapeutic option with proven benefit and acceptable toxicity to offer these women for whom there were previously no options," he added.

"If approved, practicing oncologists will have a new therapeutic option with proven benefit and acceptable toxicity."

— CHRISTOPHER TWELVES, MD

TABLE 1

EMBRACE trial Rx arms

Arm I: Eribulin at 1.4 mg/m2 over 2-5 minutes by IV on days 1 and 8 of a 21-day cycle in 508 patients

Arm II: Treatment of physician's choice (TPC) in 254 patients

The FDA recently granted eribulin (see Fact box) priority review for the treatment of women with locally advanced or metastatic breast cancer who have been previously treated with two different types of chemotherapy drugs. The FDA review will be based on the results of the global trial, which randomized 762 patients with advanced breast cancer to two treatment arms (see Table 1).

Study looks at eribulin combo and dosing

A phase I dosing study sought to establish the maximum tolerated dose (MTD) for eribulin in combination with carboplatin. Patients with advanced solid tumors whose prior standard therapy failed were enrolled. The investigators studied three different combinations and found that eribulin mesylate at 1.1 mg/m2 plus carboplatin (AUC 6) offered the MTD with dose-limiting toxicities of febrile neutropenia and/or neutropenia. An extension arm with this combination is currently enrolling patients with chemotherapy-naive, advanced non-small-cell lung cancer (ASCO 2010 abstract 2589).

Patients receiving treatment of physician's choice (TPC) were allowed to receive any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for the treatment of cancer or supportive care only. The majority of these patients (96%) received chemotherapy including vinorelbine (Navelbine), gemcitabine (Gemzar), capecitabine (Xeloda), taxanes, anthracyclines, or other chemotherapy drugs. The remainder received hormonal therapy. No patients received biologic agents or best supportive care only (ASCO 2010 abstract CRA1004; Clin Breast Cancer 10:160-163, 2010).

All patients in the study had locally recurrent or metastatic breast cancer and had undergone two to five prior chemotherapy regimens for advanced disease that included the use of an 'anthracycline and a taxane. Patients also had to have disease progression within six months or less of the last chemotherapy treatment; neuropathy, if any, less than grade 2; and Eastern Cooperative Oncology Group (ECOG) score ≤ 2. Patient and disease characteristics were similar between the two treatment groups (see Table 2).